Fig. 3: mTOR/PI3K and BET proteins are targets for AH-to-CH phenopushing.

a Enriched targets (by gene name) from overrepresentation analysis of hit compounds. Adjusted p values are calculated by hypergeometric distribution overrepresentation analysis followed by Benjamini–Hochberg procedure correction. Bars: hit (red) or non-hit (gray) compound counts per target; Blue squares: adjusted p-values for overrepresentation analysis. b–d Hit rates of screened compounds annotated as targeting b mTOR, c PI3Ks and d BET proteins in different potency ranges (represented by IC₅₀). For PI3Ks and BET proteins, the median IC₅₀ across isoforms was used. e Cellular pS6 (at S235/S236), f cellular pAKT (at S473) and g Nuclear pPol II (at S2) in normoxia (N), acute hypoxia (AH, 1 d) and chronic hypoxia (CH, 6 d). Quantification of immunofluorescence intensity (well-level average of per-cell mean intensity) and representative images are shown for e cellular pS6 (at S235/S236), f cellular pAKT (at S473), or g nuclear pPol II (at S2). Data are shown as mean ± SD from 4 biological replicates for e–g. One-way ANOVA followed by Tukey’s post hoc test: * in f: p = 0.0149, ** in g: p = 0.001, *** in f: p = 0.0001, **** in e–g: p < 0.0001. h Visualization of the effects of confirmed hits in AH on cellular pS6 (at S235/S236) (x-axis), cellular pAKT (at S473) (y-axis) and nuclear pPol II (at S2) (z-axis) based on immunofluorescence intensity (normalized to N DMSO controls). For statistical analyses, see Supplementary Data 4. Source data are provided as a Source Data file.